present invention relates to a stable, glutaraldehyde-containing pulpotomy agent and a method of using that pulpotomy agent for treating the radicular tissue of pulpotomized teeth. More particularly, the present invention relates to a composition for the treatment of affected or infected teeth prior to dental restoration involving a method of application of a glutaraldehyde-containing, stable fixative which has a long shelf life.
Pulpitis, either microbial or traumatic, is often irreversible and requires the removal of the affected or infected coronal pulp tissue. At present, the major treatment modality for cariously involved pulps of primary teeth consists of the fixation of the radicular tissue with formocresol following amputation of the coronal pulp. Formocresol, a formulation of formaldehyde and cresol in a glycerol vehicle, was introduced into dentistry in 1904 ostensibly for the purpose of neutralizing the toxins present in a necrotic pulp. The widespread use of formocresol in pediatric dentistry can be ascribed to Sweet (Sweet, C. A., "Procedure for treatment of exposed and pulpless deciduous teeth," 16 J.A.D.A. 1153 (1930)). The treatment modality he proposed entailed the sealing of a formocresol-moistened cotton pellet into the pulp chamber on three to five occasions to achieve complete fixation. That multiple-visit regime has given way to the popular five minute application which is the standard treatment even today (Doyle, et al., "Formocresol v. calcium hydroxide in pulpotomy", 29 J. Dent. Child. 86 (1962); Emmerson C. C., et al., "Pulpal changes following formocresol applications on rat molars and human primary teeth," 27 S. Calif. State Dent. Assoc. 309 (1959)). The intent of formocresol pulp therapy is to fix and kill the radicular tissue, and the ability of that therapy to accomplish that goal has been repeatedly verified and the therapy has achieved wide popularity. However, that therapy results in no healing whatsoever (Rolling, I. and H. Lambjerg-Hansen, "Pulp condition of successfully formocresol-treated primary molars," 86 Scand. J. Dent. Res. 267 (1978)), and recent evidence has demonstrated the systemic distribution of topically applied formocresol (Pashley, E. L., et al., "Systemic distribution of .sup.14 C-formaldehyde from formocresol-treated pulpotomy sites," 59 J. Dent. Res. 603 (1980)). There is also an increasing concern regarding the environmental effects of formaldehyde (Report of the Federal Panel on Formaldehyde, R. A. Griesemer, Chairman, 43 Environ. Health Prespect. 139 (1982)), raising concerns about the continued use of this pulpotomy agent.
Other agents have been investigated for use as a pulpotomy agent, including calcium hydroxide and glutaraldehyde. The latter appears to be the recommended alternative (Davis M. J., et al., "Glutaraldehyde: An alternative to formocresol for vital pulp therapy," 49 J. Dent. Child. 176 (1982); s'Gravenmade, E. J., "Some biochemical considerations of fixation in endodontics," 1 J. Endod. 233 (1975)). Glutaraldehyde is known to be an excellent fixative, serving as the standard fixative for electron microscopy, and as an effective disinfectant (Stonehill, A. A., et al., "Buffered glutaraldehyde: A new chemical sterilizing solution," 20 Am. J. Hosp. Pharm. 458 (1963)).
In spite of the proven ability of glutaraldehyde to function as a neutral fixative, there are disadvantages and limitations which have prevented the widespread use of glutaraldehyde as a pulpotomy agent. The most serious of these limitations is a result of the chemical properties of glutaraldehyde. In aqueous solution, glutaraldehyde is mildly acidic, relatively inert, and very stable. Elevation of the pH of an aqueous glutaraldehyde solution increases the microbicidal action of the glutaraldehyde (Stonehill, et al., supra). Unfortunately, at high pH, glutaraldehyde polymerizes, thereby losing that microbicidal activity. A buffer can be used to maintain the pH of the solution at a mildly alkaline level, i.e., at near physiological pH, and sodium phosphate buffer has been used for that purpose, (Ranly, D. M. and E. P. Lazzari, "A biochemical study of two bifunctional reagents as alternatives to formocresol," 62 J. Dent. Res. 1054 (1983)). A sodium bicarbonate buffer can also be used for that purpose, however the results are less satisfactory because that buffer reacts too easily with the protons that are available in the solution to form carbon dioxide, decreasing buffering capability. However, even in a buffered, mildly alkaline solution, glutaraldehyde loses microbial activity eventually as a result of increased polymerization over time, thereby limiting the shelf life of the solution. Such solutions are also sensitive to temperature; exposure to heat increases polymerization such that aqueous glutaraldehyde solutions are routinely stored at cold temperature even for short periods of time.
One alternative that can be utilized to overcome that instability is to prepare a fresh glutaraldehyde solution, buffered to the proper pH, immediately before use of the reagent as a fixative for each pulpotomy procedure. However, a solution which can be used directly without the need for further mixing or additional constituents is far preferable for convenience and has the further advantage of eliminating the potential for addition of improper proportions or incorrect constituents at the time of use. It is, therefore, an object of the present invention to provide a glutaraldehyde-containing pulpotomy agent which retains a high level of fixative activity for long periods of time, thereby insuring that it is immediately and conveniently, available for the effective fixation of tissues and the treatment of infected pulp tissue.
Another object of the present invention is to provide a glutaraldehyde-containing pulpotomy agent which embodies the requisite degree of safety, efficacy, and stability to be capable of fixing a superficial zone of radicular tissue without additional local or systemic effects and which can be stored for long periods of time.
It is another object of the present invention to provide a pulpotomy agent which is compatible with the dental materials which are usually used to restore pulpotomized teeth to form and function.
It is another object of the present invention to provide a composition for use as a pulpotomy agent comprising an aqueous solution of glutaraldehyde, an anti-oxidant, and a buffer capable of maintaining an alkaline pH.
Another object of the present invention is to provide a pulpotomy agent which is a strong fixative that can cross-link toxins, autolytic enzymes, and necroti pulp, can suppress cell activity to minimize internal resorption, is non-diffusible, exhibits low immunogenicity, is non-mutagenic, and is non-carcinogenic.